Cyteir Overview

DNA damage and genomic instability are hallmarks of cancer. This makes the disease-causing cells highly sensitive to drugs that target specific DNA repair factors. This is termed synthetic lethality.

The first type of synthetic lethalityto be developed is termed loss-of-functionsynthetic lethality. This type of synthetic lethality is useful in cancers with inactivating mutations in specific DNA repair factors, that render the cancer cell highly dependent on remaining DNA repair. Targeting one of the remaining DNA repair pathways deprives these cells of their capacity to repair damaged DNA, leading to cancer cell death by synthetic lethality.

The second type of synthetic lethality – pioneered by our scientists – is termed gain-of-function synthetic lethality. This type of synthetic lethality is designed to workin cancers that acquire a new genetic activity that does not exist in normal cells; for example, the activation of an oncogene. This new activity creates DNA damage and cellular stress, causing a reliance on specific DNA repair pathways for cancer cell survival. Targeting these critical repair pathways leads to synthetic lethal DNA damage overload caused by the abnormal genetic activity.

To date, the only synthetic lethal therapies in the clinic are the loss-of-function type. Cyteir Therapeutics is developing the next generation of synthetic lethal therapies targeting cancers with specific gain-of-function abnormalities. Our current lead program targets RAD51 to induce synthetic lethality in diseases with a gain-of-function in the gene AID (also called AIDCA).